Phytomedicine最新文献

{"title":"Huangqi-Danshen decoction improves heart failure by regulating pericardial adipose tissue derived extracellular vesicular miR-27a-3p to activate AMPKα2 mediated mitophagy","authors":"","doi":"10.1016/j.phymed.2024.156187","DOIUrl":"10.1016/j.phymed.2024.156187","url":null,"abstract":"<div><h3>Background</h3><div>Huangqi-Danshen decoction (HDD) is a classic traditional Chinese medicine for treating heart failure. Pericardial adipose tissue (PAT) has recently gained increasing attention in cardiovascular diseases.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the effect of pericardial adipose tissue-derived extracellular vesicles on heart failure, the protective effect of HDD on myocardial remodel in heart failure rats, and identify the potential molecular mechanisms involved.</div></div><div><h3>Methods</h3><div>UPLC-MS/MS identified active components of HDD. Extracellular vesicles (EVs) from pericardial adipose tissue of sham-operated and HF rats were identified through transmission electron microscopy, nanoparticle tracking analysis and western blot. EVs were co-cultured with H9c2 cardiomyocytes in order to examine their uptake and effects. MicroRNA sequencing, dual-luciferase reporter assay and PCR were conducted for exploring specific mechanisms of EVs on hypertrophic cardiomyocytes. <em>In vivo</em>, heart failure was modeled in rats via transverse aortic constriction (TAC). <em>In vitro</em>, the hypertrophic cardiomyocyte model were established using Ang II-induced H9c2 cardiomyocytes.</div></div><div><h3>Results</h3><div>UPLC-MS/MS identified 11 active components in serum of HDD administrated rats. Echocardiography showed HDD improved cardiac function in TAC model rats. HE and Masson staining indicated HDD ameliorated myocardial hypertrophy and fibrosis. MicroRNA sequencing found that HDD treatment resulted in 37 differentially expressed miRNAs (DMEs) (<em>p</em> &lt; 0.05 and |log₂FC| ≥ 1). KEGG analysis revealed that DEMs were enriched in the AMPK signaling pathway. PCR identified miR-27a-3p with the greatest difference in AMPK-related DMEs. Dual-luciferase reporter assay and Targetscan website were utilized to identify the target relationship between miR-27a-3p and PRKAA2 (AMPKα2). The miR-27a-3p negatively regulated AMPKα2 to inhibit mitophagy mediated by PINK1/Parkin pathway. HDD inhibited miR-27a-3p secretion from failing heart pericardial adipose tissue-derived extracellular vesicles, thereby improving inflammation, cardiac function, and myocardial remodeling through above pathways.</div></div><div><h3>Conclusion</h3><div>HDD inhibited the PAT-derived extracellular vesicular miR-27a-3p in failing hearts to activate AMPK/PINK1/Parkin signaling-mediated mitophagy, which improved cardiomyocyte energy metabolism, myocardial remodeling and heart failure.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stepwise integrated strategy to explore quality markers of Qishen Yiqi dripping pills against myocardial ischemia","authors":"","doi":"10.1016/j.phymed.2024.156182","DOIUrl":"10.1016/j.phymed.2024.156182","url":null,"abstract":"<div><h3>Background</h3><div>Numerous experiments and clinical practices have demonstrated the effectiveness of Qishen Yiqi dripping pills (QSYQ) on myocardial ischemia (MI). However, the bioactive ingredients and mechanisms remain unclear, leading to huge gaps between quality control and biological effect of QSYQ. Discovering quality markers (Q-markers) based on effective components is crucial for ensuring stable quality and clinical effectiveness of QSYQ.</div></div><div><h3>Purpose</h3><div>To explore Q-markers of QSYQ against MI by a stepwise strategy integrating serum pharmacochemistry, network pharmacology, metabolomics, quantitative analysis, and cell experiments.</div></div><div><h3>Methods</h3><div>Firstly, liquid/gas chromatography-mass spectrometry was applied to characterize chemical profiles of QSYQ <em>in vitro</em> and <em>in vivo</em>. Based on the serum migrating constituents, a component-target-MI interaction network was constructed. Subsequently, pharmacodynamics and metabolomics were conducted to evaluate cardioprotective effect and potential mechanism of QSYQ. Next, conjoint analysis of network pharmacology and metabolomics was performed to screen candidate Q-markers. Finally, the measurability and bioactivity were validated to justify their usage as Q-markers.</div></div><div><h3>Results</h3><div>A total of 97 components were identified in QSYQ, 24 prototypes of which were detected in serum. The “component-target-disease” interaction network was constructed based on serum migrating constituents. Pharmacodynamic results showed that QSYQ effectively improved cardiac function, attenuated inflammatory cell infiltration, alleviated myocardial fibrosis, and reduced the levels of myocardial enzymes and oxidative stress in MI rats. Metabolomics study demonstrated that 59 metabolites were markedly altered in MI rats, 25 of which were significantly reversely regulated by QSYQ. After integrative analysis of network pharmacology and metabolomics, 12 components were selected as candidate Q-markers of QSYQ, and the contents were quantified. These candidate Q-markers displayed synergistic protective effects against H₂O₂-induced injury in H9c2 cells. Taken together, 12 components with properties of transitivity and traceability, effectiveness, measurability, and compatibility contribution were defined as representative Q-markers of QSYQ, including Astragaloside IV, Ononin, Calycosin, Formononetin, Rosmarinic acid, Cryptotanshinone, Salvianolic acid A, Tanshinol, Ginsenoside Rb1, Ginsenoside Rg1, Nerolidol, and Santalol.</div></div><div><h3>Conclusion</h3><div>In this study, a novel stepwise integrated strategy was presented for discovering Q-markers related to therapeutic effects of traditional Chinese medicine prescriptions. Twelve comprehensive and representative Q-markers of QSYQ were identified for the first time to improve its quality control.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huangqi Jianzhong decoction improves gastric intestinal metaplasia in rats by regulating the gut‒thyroid axis","authors":"","doi":"10.1016/j.phymed.2024.156174","DOIUrl":"10.1016/j.phymed.2024.156174","url":null,"abstract":"<div><h3>Background</h3><div>Gastric intestinal metaplasia (GIM) is a crucial stage in the progression of gastric cancer. Huangqi Jianzhong decoction (HQJZ) has emerged as a leading therapeutic strategy for treating GIM patients with cold intolerance in traditional Chinese medicine clinics, but the detailed mechanism remains poorly understood.</div></div><div><h3>Objective</h3><div>The present study aimed to elucidate the molecular mechanism by which HQJZ alleviates GIM in a rat model on the basis of the gut microbiota‒thyroid axis.</div></div><div><h3>Methods</h3><div>A GIM rat model was established by administering cold salicylic acid and sodium deoxycholate (SDC) for 12 weeks, followed by gavage treatment with HQJZ for an additional four weeks. Lianpu Yin (LPY) was used as a comparison formula. The cold tolerance characteristics of GIM rats were evaluated using cold tolerance and temperature‒tropism experiment experiments. Thyroid pathological changes were evaluated with HE staining, and thyroid function was measured via quantification of T3 and T4 levels with ELISA. The gut microbiota was analyzed using 16S rRNA gene sequencing, and fecal butyric acid and serum metabolites were quantified utilizing metabolomics. The key molecular mechanism was verified in the Nthy-ori 3–1 cell model.</div></div><div><h3>Results</h3><div>HQJZ, but not LPY, significantly improved gastric mucosa and thyroid tissue lesions in GIM rats, increased the serum levels of the thyroid hormones T3 and T4, and enhanced cold tolerance. HQJZ treatment promoted the enrichment of fecal butyrate-producing bacteria, specifically the bacteria <em>Allobaculum</em> and <em>Bifidobacterium</em>, resulting in a marked increase in fecal butyric acid concentrations. HQJZ treatment significantly diminished the levels of mitochondrial damage-related serum metabolites, including p-cresol sulfate and indoxyl sulfate. Mechanistically, <em>in vivo</em> investigations further demonstrated that butyric acid not only improved thyroid tissue lesions but also restored the fecal microbiota structure, as well as low-temperature tropism, in GIM rats. Furthermore, butyrate diminished the mitochondrial damage induced by SDC in these cells, as evidenced by decreased reactive oxygen species levels and increased ATP production and mitochondrial membrane potential. Importantly, <em>in vitro</em> studies revealed that butyrate protected against SDC-induced injury in Nthy-ori 3–1 cells through the upregulation of TG, TPO, and TSHR expression.</div></div><div><h3>Conclusions</h3><div>HQJZ promotes cold tolerance and improves thyroid function in GIM rats by enriching gut butyrate-producing bacteria.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Xue-Jie-San treating Crohn's disease complicated by atherosclerosis: Network pharmacology, molecular docking and experimental validation","authors":"","doi":"10.1016/j.phymed.2024.156169","DOIUrl":"10.1016/j.phymed.2024.156169","url":null,"abstract":"<div><h3>Background</h3><div>Crohn's disease (CD), as a chronic systemic inflammatory disease, is strongly associated with the development of premature atherosclerosis (AS). Atherosclerotic cardiovascular disease, including coronary heart disease, myocardial infarction and stroke, is a lethal complication of CD. Nowadays, there is a lack of effective monotherapy for CD complicated by AS.</div></div><div><h3>Purpose</h3><div>To explore the underlying effects and mechanisms of Xue-Jie-San (XJS) on treating CD complicated by AS via network pharmacology and experimental validation.</div></div><div><h3>Methods</h3><div>The targets of XJS components were obtained from TCMSP, ETCM and PubChem databases as well as the disease genes of CD and AS from GeneCards, DisGeNET and OMIM databases. The core targets were screened out from the drug-disease common targets identified by protein–protein interaction (PPI) network analysis and then analyzed with GO and KEGG enrichment. The interaction between core target and XJS component was detected by molecular docking and molecular dynamics simulation. Subsequently, the core targets were validated via GEO datasets and their biological functions were confirmed <em>in vitro</em>. Nile red staining was used to evaluated lipid accumulation in human umbilical vein endothelial cells (HUVECs) challenged by lipopolysaccharide (LPS) combined with oxidized low-density lipoprotein (ox-LDL). Levels of pro-inflammatory cytokines were examined by enzyme-linked immunosorbent assay. Chemokine CCL2 and CXCL8 were detected by immunofluorescence staining. The activity of the TLR4/Myd88/NF-κB signaling pathway was assessed using Western blot.</div></div><div><h3>Results</h3><div>In total, 26 common target genes of XJS, CD and AS were found. Among them, 11 core genes were identified by PPI network analysis. The effects of XJS treating CD complicated by AS were mainly mediated by the lipid and atherosclerosis pathway, inflammatory bowel disease pathway and toll-like receptor signaling pathway. Molecular docking and molecular dynamics simulation displayed strong binding affinity between XJS component and the core target. Six core genes including <em>TLR4, IL-1β, TNF, ICAM1, CCL2</em> and <em>CXCL8</em> were validated by GEO datasets. <em>In vitro</em>, the effects of XJS on reducing lipid accumulation, secretion of IL-1<em>β</em>, IL6, TNF-α, CCL2 and CXCL8, and the protein expressions of TLR4, Myd88, p-p65 and ICAM1 were verified.</div></div><div><h3>Conclusion</h3><div>XJS is a potential candidate drug for the treatment of CD complicated by AS. The underlying mechanisms involve mitigation of lipid accumulation-mediated endothelial dysfunction and blockage of immune inflammatory response by targeting TLR4.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics and network pharmacology approaches reveal Gui-Ling-Ji alleviates oligoasthenoteratozoospermia by regulating arachidonic acid pathway","authors":"","doi":"10.1016/j.phymed.2024.156184","DOIUrl":"10.1016/j.phymed.2024.156184","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Gui-Ling-Ji (GLJ) described in the ancient medical book 'Yunji Qijian' is a traditional Chinese medicine formula used to improve male fertility. It is now available for the treatment of oligoasthenoteratozoospermia (OAT). However, the active ingredients and mechanism of GLJ are not clear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The aim of this study was to clarify the active ingredients and mechanism of GLJ in OAT.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Firstly, the cyclophosphamide-induced OAT rat model was established to evaluate the efficacy of GLJ. Secondly, serum/urine-based metabolomics and lipidomics and tissue-based transcriptomics were performed to discover the differential metabolites and genes in rats. Furthermore, network pharmacology was constructed to explore the associated mechanisms based on the results of multi-omics analysis. Finally, cellular experiment on testicular mesenchymal stromal cells (TM3) was used to validate the active ingredients and the key metabolic pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Rats were administered GLJ by gavage every day for 3 weeks. Testicular damage and weight loss caused by cyclophosphamide were restored in rats, the sperm count and motility were improved, and levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) secretion were also elevated. Compared to the metabolites of OAT rats, 51 and 37 differential metabolites regulated by GLJ were identified from serum and urine respectively, 54 lipid differential metabolites regulated by GLJ were identified by lipidomics. At the same time, 23 of the 258 differential genes were found to be regulated by OAT rats and then reverse-regulated by GLJ. Network pharmacology has identified 13 pathways (Steroid hormone biosynthesis, Taurine and hypotaurine metabolism, Primary bile acid biosynthesis, Linoleic acid metabolism, Retinol metabolism, Glycerophospholipid metabolism, Ether lipid metabolism, Sphingolipid metabolism, Arachidonic acid metabolism, Glutathione metabolism, Arginine biosynthesis, Arginine and proline metabolism, D-Arginine and D-ornithine metabolism), four metabolites (arachidonic acid, oestrone sulphate, phosphatidylglycerol choline and sphingomyelin) and 15 targets (ABCB11, ALDH18A1, CCL3, CD244, CIITA, CYP2C8, DLL1, ITGA4, ESR1, AR, ABCB1, ABCC1, ALB, PLA2G1B and NOS2). GLJ, psoralen, isopsoralen, liquiritin, isoliquiritin, liquiritigenin, and ginsenoside Ro could significantly promote T secretion from TM3 cells. Additionally, arachidonic acid metabolism particularly the cyclooxygenase pathway, is closely related to the promotion of testosterone secretion by GLJ in TM3.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;GLJ has a therapeutic efficacy in cyclophosphamide-induced OAT rats, which can modulate the disorders of lipid metabolism and amino acid metabolism. Arachidonic acid metabolism may be a key pathway, and six prototype compounds are potential key active ingredients for GLJ.&lt;","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prebiotic inulin alleviates anxiety and depression-like behavior in alcohol withdrawal mice by modulating the gut microbiota and 5-HT metabolism","authors":"","doi":"10.1016/j.phymed.2024.156181","DOIUrl":"10.1016/j.phymed.2024.156181","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol dependence (AD) is a common psychiatric disorder, often accompanied by anxiety and depression. These comorbidities are linked to disturbances in serotonin (5-HT) metabolism and gut microbiota dysbiosis. Clinical studies suggest that inulin, a prebiotic, can alleviate anxiety and depression in AD patients by affecting the gut microbiota, although the mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>The purpose of this study is to investigate the potential mechanisms by which inulin, a prebiotic, improves anxiety and depression-like behaviors in AD withdrawal mice. This research is based on the drug and food homology and intestinal treatment of encephalopathy, with the goal of developing new clinical strategies for AD treatment.</div></div><div><h3>Study Design</h3><div>For this purpose, fecal samples from AD patients were analyzed to identify microorganisms associated with AD. An AD withdrawal mouse model was created, with inulin as the intervention and fluvoxamine maleate as the control. Techniques such as 16S microbiome sequencing and UPLC-TQMS-targeted metabolomics were used to assess gut microbiota, short-chain fatty acids (SCFAs) levels, and 5-HT metabolism.</div></div><div><h3>Methods</h3><div>The AD withdrawal model was built using the \"Drinking-in-the-dark\" protocol over 6 weeks. Inulin (2 g/kg/day) and fluvoxamine maleate (30 mg/kg/day) were administered for 4 weeks. The open field test, forced swim test, and tail suspension test were used to evaluate anxiety and depression-like behaviors in mice. ELISA and qRT-PCR assessed 5-HT metabolism in the colon, blood, and prefrontal cortex, while 16S microbiome sequencing analyzed changes in gut microbiota and UPLC-TQMS examined SCFAs levels. Immunohistochemistry was used to study intestinal barrier integrity.</div></div><div><h3>Results</h3><div>AD patients showed reduced SCFA-producing bacteria such as <em>Faecalibacterium</em> and <em>Roseburia</em>. In mice, AD withdrawal led to anxiety and depression-like behaviors, disrupted 5-HT metabolism, and gut microbiota dysbiosis. Inulin supplementation alleviated these behaviors, increased 5-HT and 5-hydroxytryptophan (5-HTP) levels, upregulated colonic <em>tryptophan hydroxylase 1</em> (TPH1) expression, and promoted the growth of beneficial bacteria such as <em>Faecalibacterium</em> and <em>Roseburia</em>, while also increasing SCFAs levels.</div></div><div><h3>Conclusion</h3><div>Inulin increases the abundance of <em>Faecalibacterium</em> and <em>Roseburia</em>, enhances SCFAs production, and regulates 5-HT metabolism, improving anxiety and depression-like behaviors in AD withdrawal mice. These findings suggest that inulin may serve as a nutritional intervention for mental health in AD patients by targeting the microbiome-gut-brain axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective effects of medicinal plants against cigarette smoking: A comprehensive review.","authors":"Jamshid Tabeshpour, Amirali Asadpour, Sayena Norouz, Hossein Hosseinzadeh","doi":"10.1016/j.phymed.2024.156199","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156199","url":null,"abstract":"<p><strong>Backgrounds: </strong>Cigarette smoking remains a pervasive and harmful habit, and it poses a significant public health concern globally. Tobacco smoke contains numerous toxicants and carcinogens that contribute to the incidence of various diseases, including respiratory ailments, cancer, and cardiovascular disorders. Over the past decade, there has been a growing interest in exploring natural remedies to mitigate the harmful effects of cigarette smoke (CS). Medicinal plants, with their rich phytochemical compositions, have emerged as potential sources of protective agents against CS-induced damage.</p><p><strong>Objectives: </strong>The current review attempts to comprehensively review and provide a thorough analysis of the protective effects of medicinal plants, including ginseng, Aloe vera, Olea europaea, Zea mays, green tea, etc. against CS-related toxicities.</p><p><strong>Materials and methods: </strong>A comprehensive research and compilation of existing literature were conducted. We conducted a literature search using the Web of Science, PubMed, Scopus, and Google Scholar. We selected articles published in English between 1987 and 2025. The search was performed using keywords including cigarette smoking, cigarette smokers, second-hand smokers, natural compounds, plant extracts, naturally derived products, natural resources, phytochemicals, and medicinal plants.</p><p><strong>Results: </strong>This review critically investigated recent literature focusing on the effects of medicinal plant extracts, essential oils, and isolated compounds on reducing the adverse consequences of CS exposure. These investigations encompassed several in vivo, in vitro, and clinical trials, clarifying the mechanisms underlying the protective effects of these plants. The notable antioxidant, anti-inflammatory, and detoxifying properties of these botanical interventions were also highlighted.</p><p><strong>Conclusion: </strong>Collectively, this review emphasizes the potential of medicinal plants in alleviating the harmful effects of CS. The rich active constituents present in these plants offer various mechanisms that counteract oxidative stress, inflammation, and carcinogenesis induced by CS exposure. Further research is warranted to reveal the precise molecular mechanisms, derive dosing recommendations, and explore the efficacy of botanical interventions in large-scale clinical trials, ultimately improving public health outcomes and providing valuable insights for the smoking population worldwide.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinacoside inhibits tumor immune evasion by downregulating inducible PD-L1 and reshaping tumor immune landscape in breast and colorectal cancer.","authors":"Xiaoyu Wang, Binxin Tan, Jiazhou Liu, Jing Wang, Mingjing Chen, Qian Yang, Xiang Zhang, Fan Li, Yuxian Wei, Ke Wu, Guosheng Ren, Hongzhong Li","doi":"10.1016/j.phymed.2024.156188","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156188","url":null,"abstract":"<p><strong>Background: </strong>Targeting PD-L1 has become a crucial approach in tumor immunotherapy. Echinacoside (ECH) is a natural compound known for its extensive biological activities, its impact on antitumor immunity remains uncertain.</p><p><strong>Purpose: </strong>This work was designed to assess the effects of ECH on the PD-L1/PD-1-mediated tumor immune evasion and its underlying mechanisms.</p><p><strong>Methods: </strong>Flow cytometry and RT-qPCR were utilized to explore the influence of ECH on PD-L1 expression. Western blot was employed to examine the mechanism by which ECH might modulate PD-L1 expression. Flow cytometry was conducted to evaluate the influence of ECH therapy, or the synergistic effects of ECH combined with immune checkpoint blockade (ICB) on tumor immune microenvironment (TIME) in tumor-burden mice. Blood biochemistry tests were used to evaluate the safety of ECH treatment.</p><p><strong>Results: </strong>ECH downregulated both the protein and mRNA expression levels of IFN-γ-induced PD-L1 through JAK/STAT1/IRF1 signaling pathway. ECH treatment upregulated the infiltration of IFN-γ⁺CD8⁺ T cells and Ki-67⁺CD8⁺ T cells, lowered the frequency of TIM-3⁺PD-1⁺ T cells, promoted the infiltration of effector CD4⁺ T cells and total CD8⁺ T cells while suppressed the percentage of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Moreover, the combination of ECH and anti-PD-1 or anti-CTLA-4 therapy exhibited synergistic anti-tumor effects, reshaping TIME. Blood biochemistry tests unveiled that ECH did not show additional toxicity.</p><p><strong>Conclusion: </strong>ECH upregulates the expression of inducible PD-L1 through the JAK/STAT1/IRF1 signaling pathway, enhances T cell function, and reshapes the tumor immune landscape into an anti-tumor phenotype. Importantly, ECH markedly enhances the efficacy of ICB treatment, indicating its potential application in anti-tumor therapy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of METTL3-mediated CircStk4 modification in the treatment of chronic glomerulonephritis with Qi Teng Xiao Zhuo granule.","authors":"Xiujuan Qin, Huiyu Chen, Wenjia Zheng, Wenjie Hu, Xianjin Xu, Jiarong Gao","doi":"10.1016/j.phymed.2024.156183","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156183","url":null,"abstract":"<p><strong>Background: </strong>Qi Teng Xiao Zhuo granule (QTXZG), a compound preparation used in traditional Chinese medicine, is a highly effective treatment for chronic glomerulonephritis (CGN). Previously, the mechanism of circStk4 and the N⁶-methyladenosine (m⁶A) modification of circStk4 in CGN was elucidated in vivo. Nevertheless, there hasn't been any research done on the connection between circStk4 and QTXZG's mechanism in CGN treatment.</p><p><strong>Purpose: </strong>The current study intended to clarify the molecular mechanism of QTXZG in CGN therapy by both in vitro and in vivo investigations.</p><p><strong>Methods: </strong>Mouse mesangial cells (MMCs) were used to measure the rate of proliferation and apoptosis using flow cytometry and the Cell Counting Kit-8 (CCK-8) assay. The expression of markers associated with proliferation, apoptosis, and autophagy was analysed using reverse transcription quantitative PCR (RT-qPCR), western blotting (WB), and immunofluorescence (IF), respectively. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was utilized to analyse the m⁶A modification of circStk4, and METTL3 expression was assessed using RT-qPCR. Subsequently, miR-133a-3p and C1 expression was examined using RT-qPCR, WB, and IF. Adeno-associated virus 9 (AAV9)-circStk4 knockdown vector and a METTL3 inhibitor were used to explore the roles of METTL3 and circStk4 in CGN. Additionally, molecular docking and cellular thermal shift assays (CETSAs) were performed to assess the binding affinity between METTL3 and the active compounds in QTXZG.</p><p><strong>Results: </strong>Mechanistically, QTXZG reduced METTL3 expression and decreased circStk4 m⁶A levels while decreasing circStk4 levels and regulating the miR-133a-3p/C1 axis. Functionally, QTXZG inhibited MMCs and renal tissue proliferation, promoted apoptosis and autophagy, and reduced inflammation. In vivo experiments further confirmed that downregulated ircStk4 and METTL3 expression were accompanied by the therapeutic effects of QTXZG, resulting in a significant attenuation of renal injury, reduction in inflammation, inhibition of renal tissue proliferation and promotion of apoptosis and autophagy.</p><p><strong>Conclusion: </strong>The present study revealed that QTXZG reduced circStk4 m⁶A and METTL3 expression to regulate the circStk4/miR-133a-3p/C1 axis in the treatment of CGN and thus inhibited glomerular tissue/membrane cell proliferation and promoted autophagy and apoptosis; these results uncovered a new mechanism by which QTXZG reduced CGN and imply that METTL3 might be a target for innovative therapeutic approaches.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suyin Detoxification Granule alleviates trimethylamine N-oxide–induced tubular ferroptosis and renal fibrosis to prevent chronic kidney disease progression","authors":"","doi":"10.1016/j.phymed.2024.156195","DOIUrl":"10.1016/j.phymed.2024.156195","url":null,"abstract":"<div><h3>Background</h3><div>Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is a risk factor for chronic kidney disease (CKD) progression. Suyin Detoxification Granule (SDG) is a traditional Chinese medicine preparation that has been proven to significantly reduce renal function damage and serum TMAO levels in patients with CKD. However, its specific mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study investigated the role of TMAO-induced ferroptosis in CKD, and further explored the mechanism of SDG in improving TMAO-induced kidney injury.</div></div><div><h3>Methods</h3><div>A TMAO renal tubular epithelial cell injury model was constructed in vitro. After using freeze-dried powder of Suyin Detoxification Prescription (SDP), proteomic analysis, Western blotting, ferroptosis phenotype-related detection, and ELISA were performed to explore its mechanism. In vivo, a adenine-induced CKD model was established, with or without a high-choline diet to observe the impact of TMAO on CKD, and SDG or 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) was used for intervention. The composition of gut microbiota was analyzed using 16SrRNA sequencing, and the effect of SDG on gut-derived TMAO-induced kidney injury under the background of CKD was evaluated by pathological staining, immunoblotting, immunohistochemistry, and fluorescence staining.</div></div><div><h3>Results</h3><div>In vitro, TMAO could induce ferroptosis and secrete profibrotic factors in NRK-52E cells. SDP could inhibit TMAO-induced ferroptosis and reduce the secretion of profibrotic factors. The amelioration of ferroptosis by SDP was also verified in RSL3-induced cells. In vivo, our results demonstrated that gut-derived TMAO could promote CKD progression by inducing tubular ferroptosis, profibrotic factors expression and renal fibrosis. In addition, we illustrated that SDG might reduce circulating TMAO levels by down-regulating the gut microbiota related to TMAO (including Muribaculaceae, Bacteroides and Ruminococcaceae_UCG-010). Furthermore, SDG could prevent CKD progression by reducing TMAO-induced renal damage.</div></div><div><h3>Conclusion</h3><div>SDG reduced circulating TMAO levels by regulating gut microbiota and inhibited TMAO-induced renal tubular ferroptosis, profibrotic factors secretion, and renal fibrosis to prevent CKD progression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}